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Massachusetts Institute of Technology (MIT)engineers have developed a new model of liver tissue to help reveal the stages of liver regeneration in hopes of helping people with liver disease, according to a new study published in the journal Proceedings of the National Academy of Sciences. Researchers said that by finding an effective way to stimulate the liver to regenerate on its own, some liver transplants could potentially be avoided and it could help a donated liver grow after being transplanted, according to a statement from MIT press.
Liver experts told Fox News that most patients who need liver transplants are often those who have been diagnosed with chronic conditions such as viral hepatitis, primary biliary cholangitis (PBC), cancer or fatty liver disease. Researchers hope that by learning to use the regenerative properties of the liver, doctors will have more options for treating chronic liver disease.
According to MIT, even if 70% of the liver is removed, the remaining tissue can still grow back to its full size within a few months. Meredith Stone is a 50-year-old medical professional who was diagnosed with primary biliary cholangitis, an autoimmune disease that attacks the liver’s bile ducts and damages the liver. Stone was not part of the study but shared that she now has cirrhosis of the liver, despite not having drunk alcohol in over 20 years. Stone told Fox News that she is currently taking drugs such as ocaliva and ursodial in hopes of slowing the progression of the disease and preventing a liver transplant.
“I heard about this study and prayed that these researchers would find a way to help the liver regenerate. It would give such peace of mind.” Stone added, “Not much research is being done on PBC and I just hope they find a way to help my liver regenerate and other people struggling with devastating liver disease.”
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The researchers used mouse studies to understand the regenerative pathways that occur after liver injury or disease. According to the report, a key factor is the reciprocal relationship between cells found in the liver called hepatocytes and cells that line blood vessels called endothelial cells. The researchers explained that hepatocytes produce factors that help blood vessels grow, and endothelial cells generate growth factors that help hepatocytes proliferate. The researchers also said that previous studies in mice found blood flow to be another component of liver regeneration.
The MIT researchers wanted to model liver regenerative interactions, so they teamed up with Christopher Chen, MD, PhD, distinguished William F. Warren Professor of Biomedical Engineering at Boston University, who designs microfluidic devices with channels which act as blood vessels.
The researchers grew blood vessels along one of these microfluidic channels, then added aggregates derived from liver cells taken from human organ donors.
They developed a chip designed so that molecules such as growth factors could flow between blood vessels and liver spheroids, according to the release. This design allowed researchers to knock out genes from specific cell types and see how this affects the overall regeneration process.
Sangeeta Bhatia, a fellow at the Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science at MIT, said in the statement, “For years people have identified different genes that appear to be involved in mouse liver regeneration and some of them seem to be important in humans, but they never managed to understand all the signals to make human liver cells proliferate.”
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This ‘regeneration on a chip’ model showed that increasing fluid flow alone did not stimulate liver cell division, which is part of the cycle involved in liver regeneration. But they found that if they also provided an inflammatory signal, called the cytokine IL-1-beta, liver cells entered the dividing cycle, according to the release.
The researchers also blocked a gene in endothelial cells responsible for making prostaglandin E2 (PGE2), a molecule also involved in liver regeneration in zebrafish. By blocking the gene in these cells, they were able to demonstrate that this molecule stimulates human liver cells to enter the cell division cycle, according to the report.
The team plans to explore other growth factors and molecules that are produced in their model during liver regeneration. They also hope to find the signals that tell the liver when to stop regenerating.
“Right now, when patients come in with liver failure, you have to transplant them because you don’t know if they’re going to recover on their own. But if we knew who had a robust regenerative response, and if we just needed to stabilize them for a little while, we could spare these patients a transplant,” Bhatia said in the MIT statement.
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Bhatia hopes the team of researchers will be able to harness molecules to help treat patients with liver failure. Investigators also said another possibility is that doctors could potentially use biomarkers to determine the likelihood of a patient’s liver growing back on its own.
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